The broad objective of this research program is to gain understanding into the nature of the disorder, diabetes mellitus, particularly with respect to etiology, and to mechanisms of pathological, physiological, and biochemical changes. The proposed program will focus on thee major interrelated areas: (1) insulin secretion and action; (2) primary cellular abnormalities in diabetes; and (3) pathophysiological abnormalities in diabetes. Five research projects are proposed. Studies range from the molecular and cellular level to physiological investigation of the whole organism.